Ovarian binding and intrinsic biological activity of desialylated human chorionic gonadothrophin (ASIALO-hCG).

The present study was undertaken to investigate the effect of desialylation on the intrinsic in vivo biological activity of hCG. To block the hepatic uptake of asialo-hCG we investigated asialo-orosomucoid. The biological activity of hCG and asialo-hCG was estimated with the ovarian ascorbic acid depletion assay (OAAD). The uptake studies were performed with [125I]hCG and [125I]asialo-hCG. Desialylation of hCG increased its hepatic uptake, almost completely abolished its ovarian uptake, and reduced its in vivo biological activity to less than 1%. Administration of asialo-orosomucoid caused a reduction of the hepatic uptake of asialo-hCG to the level observed for hCG. The ovarian uptake increased, but was lower than observed for hCG, due to a considerably higher renal accumulation of asialo-hCG. The in vivo biological activity of asialo-hCG was approximately 1/5 of the activity of hCG when both were tested in the presence of asialo-orosomucoid. To exclude the interference of renal accumulation, binding and biological activity were also investigated after bilateral nephrectomy. The uptake of radioactivity in the ovaries following injection of [512I]asialo-hCG and asialo-orosomucoid was then almost the same as observed after injection of [125I]hCG alone. When both preparations were now tested in the presence of asialo-orosomucoid, the in vivo biological activity of asialo-hCG appeared to be approximately 1/3 of the value obtained for hCG. It is concluded that the intrinsic in vivo biological activity of hCG is lowered by desialylation.